A Center for Clinical Research on Opioid and Cocaine Abuse will be organized to develop new understanding of and treatment approaches to such abusers. To achieve this goal, we will conduct a programmatic series of research investigations in humans, provide training and research opportunities for new investigators with a range of professional disciplines, and stimulate interchange among investigators from different sections of the Yale Medical Center as they focus on problems of cocaine and opioid abuse. The Center will consist of three Divisions linked by Core facilities and staff: a. Treatment Research Division--development and testing of innovative treatment approaches for cocaine and opioid abuse, b. Neurobiology Division--investigation of neurobiological correlates of opioid and cocaine use and withdrawal in humans, c. Epidemiology Division--identification of clinically significant subgroups within the population of opioid and cocaine abusers. The Core staff will be charged with: a. Monitoring the quality and guiding the direction of disparate research endeavors within the Center as well as providing consultation and assistance in the conduct of the Center's major research projects, b. Coordinating training efforts by supervising trainees, providing research seminars, and providing technical and material assistance in trainee's research projects, and c. stimulating and supporting the conduct of pilot and/or small research projects by both trainees and faculty members. With this application we describe the first four major investigations to be undertaken through the Center including: 1. the first comprehensive study in humans to assess the transition of opioid abusers from agonist to agonist/antagonist to antagonist which would improve our ability to get patients off methadone maintenance and onto antagonist. 2. an evaluation of the acute effects of cocaine on patients undergoing treatment with Naltrexone, Methadone, or tricyclic antidepressants, which could suggest new perspectives on the use of these agents, 3. an evaluation of receptor and neurobiological changes in withdrawal from opioids which could provide a more comprehensive understanding of the withdrawal process, and 4. a study of the relationship between quality of parenting and psychopathology in opioid addicts which could lead to the development of strategies to prevent morbidity in opioid addicts' children.